Amyloid fibril formation and deposition is a common feature of a wide range of fatal diseases including spongiform encephalopathies, Alzheimer's disease, and familial amyloidotic polyneuropathies (FAP), among many others. In certain forms of FAP, the amyloid fibrils are mostly constituted by variants of transthyretin (TTR), a homotetrameric plasma protein. Recently, we showed that transthyretin in solution may undergo dissociation to a non-native monomer, even under close to physiological conditions of temperature, pH, ionic strength, and protein concentration. We also showed that this non-native monomer is a compact structure, does not behave as a molten globule, and may lead to the formation of partially unfolded monomeric species and high molecular mass soluble aggregates (Quintas, A., Saraiva, M. J. M., and Brito, R. M. M. (1999) J. Biol. Chem. 274, 32943-32949). Here, based on aging experiments of tetrameric TTR and chemically induced protein unfolding experiments of the non-native monomeric forms, we show that tetramer dissociation and partial unfolding of the monomer precedes amyloid fibril formation. We also show that TTR variants with the least thermodynamically stable non-native monomer produce the largest amount of partially unfolded monomeric species and soluble aggregates under conditions that are close to physiological. Additionally, the soluble aggregates formed by the amyloidogenic TTR variants showed morphological and thioflavin-T fluorescence properties characteristic of amyloid. These results allowed us to conclude that amyloid fibril formation by some TTR variants might be triggered by tetramer dissociation to a compact non-native monomer with low conformational stability, which originates partially unfolded monomeric species with a high tendency for ordered aggregation into amyloid fibrils. Thus, partial unfolding and conformational fluctuations of molecular species with marginal thermodynamic stability may play a crucial role on amyloid formation in vivo.

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Health literacy, a more complex concept than knowledge, is a required capacity to obtain, understand, integrate and act on health information [1], in order to enhance individual and community health, which is defined by different levels, according to the autonomy and personal capacitation in decision making [2]. Medium levels of Health literacy in an adolescent population were found in a study conducted in 2013/2014, being higher in sexual and reproductive health and lower in substance use. It was also noticed that the higher levels of health literacy were in the area adolescents refer to have receipt more health information. The health literacy competence with higher scores was communication skills, and the lower scores were in the capacity to analyze factors that influence health. Higher levels were also found in younger teenagers, but in a higher school level, confirming the importance of health education in these age and development stage. Adolescents seek more information in health professionals and parents, being friends more valued as a source information in older adolescents, which enhance the importance of peer education mainly in older adolescents [3]. As a set of competences based on knowledge, health literacy should be developed through education interventions, encompassing the cultural and social context of individuals, since the society, culture and education system where the individual is inserted can define the way the development and enforcement of the health literacy competences [4]. The valued sources of information should be taken into account, as well as needs of information in some topics referred by adolescents in an efficient health education. Schizophrenia is a serious and chronic mental illness which has a profound effect on the health and well-being related with the well-known nature of psychotic symptoms. The exercise has the potential to improve the life of people with schizophrenia improving physical health and alleviating psychiatric symptoms. However, most people with schizophrenia remains sedentary and lack of access to exercise programs are barriers to achieve health benefits. The aim of this study is to evaluate the effect of exercise on I) the type of intervention in mental health, II) in salivary levels of alpha-amylase and cortisol and serum levels of S100B and BDNF, and on III) the quality of life and selfperception of the physical domain of people with schizophrenia. The sample consisted of 31 females in long-term institutions in the Casa de Saúde Rainha Santa Isabel, with age between 25 and 63, and with diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Physical fitness was assessed by the six-minute walk distance test (6MWD). Biological variables were determined by ELISA (Enzyme-Linked Immunosorbent Assay). Psychological variables were assessed using SF-36, PSPP-SCV, RSES and SWLS tests. Walking exercise has a positive impact on physical fitness (6MWD -p = 0.001) and physical components of the psychological test...

The role of disulfide bridges in the structure, stability, and folding pathways of proteins has been the subject of wide interest in the fields of protein design and engineering. However, the relative importance of entropic and enthalpic contributions for the stabilization of proteins provided by disulfides is not always clear. Here, we perform a detailed analysis of the role of disulfides in the conformational stability of human Interleukin-4 (IL4), a four-helix bundle protein. In order to evaluate the contribution of two out of the three disulfides to the structure and stability of IL4, two IL4 mutants, C3T-IL4 and C24T-IL4, were used. NMR and ANS binding experiments were compatible with altered dynamics and an increase of the nonpolar solvent-accessible surface area of the folded state of the mutant proteins. Chemical and thermal unfolding experiments followed by fluorescence and circular dichroism revealed that both mutant proteins have lower conformational stability than the wild-type protein. Transition temperatures of unfolding decreased 14 degrees C for C3T-IL4 and 10 degrees C for C24T-IL4, when compared to WT-IL4, and the conformational stability, at 25 degrees C, decreased 4.9 kcal/mol for C3T-IL4 and 3.2 kcal/mol for C24T-IL4. Interestingly, both the enthalpy and the entropy of unfolding, at the transition temperature, decreased in the mutant proteins. Moreover, a smaller change in heat capacity of unfolding was also observed for the mutants. Thus, disulfide bridges in IL4 play a critical role in maintaining the thermodynamic stability and core packing of the helix bundle.